1. Field of the Invention
The present invention relates to compounds containing estrogenic activity, and in particular to compounds isolated from plants and containing estrogenic activity.
2. The Prior Arts
More than half of the women who faced menopause have estrogen-deficiency related syndromes due to ovary atrophy. The symptoms include heart, blood vessel, metabolic and mentally diseases, as well as heat flush, sweats, rapid heart beat and so on. Therefore, hormone replacement therapy (HRT) was carried out in menopause women to prevent menopausal symptoms due to insufficient estrogen recently.
However, an increased association of estrogen-only HRT with endometrioid ovarian cancer was revealed in previous reports. The combination of conjugated equine estrogens (CEE) and progesterone such as medroxyprogesterone acetate (MPA) was suggested at present to prevent the chance of endometrioid ovarian cancer induced by estrogen-only HRT. However, a study of USA in 2002 showed that women in the CEE plus MPA group had higher risks of breast cancer (26%), stroke (41%), cardio disease (29%), and venous thromboembolism (113%). There were indications of health damages and side effects for those receiving therapy. Therefore, physicians were forced to search for alternative treatments. These alternatives include non-hormone chemicals, such as clonidine, venlafaxine, fluoxetine, and paroxetine, which were not only less efficient than HRT in treating menopausal symptoms, but also induced annoying side effects.
It was known from the studies of molecular biology that estrogens operate in cells through the binding of estrogen receptors (ER) to initiate the gene expression. These estrogen regulatory genes contain estrogen responsive element (ERE) in the promoter region to present their activities. A compound that binds to the ER and produces partial estrogenic effects is a partial agonist, such as diethylstilbestrol (DES). Conversely, a compound that binds to the ER and blocks binding of estrogens but does not allow the receptor to adopt a functionally active state is the to be an antagonist or an anti-estrogen, such as tamoxifen, which shows inhibitory effect on estrogen-dependent cancer. There are two types of ERs, ERα and ERβ, being identified in quite different regions. ERα expression is primarily found in the endometrium and breast and uterus. In contrast, ERβ is found mainly in brain, bone and so on. Ideal selective estrogen receptor modulators (SERMs) are ER ligands that act like estrogens in tissues of blood vessels and bones, but act weakly in mammary gland. These molecules would be of great beneficial effect in menopause women.
Therefore, development of an estrogen alternative for menopause women to improve the symptoms but without side effects related to estrogens purified from animals (such as CEE) or non-hormone therapy is in urgent need.